Taking it

Taking saquinavir (Invirase) with low dose ritonavir boosts the amount of saquinavir in the blood and ensures saquinavir stays in the body for longer. Various doses of ritonavir (Norvir)-boosted saquinavir have been tested in clinical trials, but in September 2002, European drug regulatory authorities approved twice daily saquinavir at a dose of 1000mg with 100mg ritonavir. This dose was approved in the United States in December 2003.

Ritonavir-boosted saquinavir should be taken within two hours of a meal. Saquinavir and ritonavir should be taken at the same time in order to ensure that saquinavir concentrations are boosted adequately. Saquinavir should only be used with ritonavir or with ritonavir-boosted lopinavir.

Saquinavir is available both in 200mg capsules, and in new 500mg tablets. The two formulations produce similar levels of active drug in the blood, and both require ritonavir boosting and need to be taken with food.¹ However, use of the tablet formulation reduces the number of pills that a patient needs to take every day.

Saquinavir should not be the only protease inhibitor in an antiretroviral combination. Without ritonavir boosting, less than 10% of each dose is absorbed into the bloodstream and very small quantities cross into the central nervous system. The antiviral effects of hard gel saquinavir-based combinations are significantly smaller and less sustained than those of combinations based on other protease inhibitors, unless it is taken in combination with another protease inhibitor such as ritonavir.

Saquinavir at a dose of 400mg boosted by 400mg ritonavir twice a day is also approved, but this dosage is less popular due to its greater frequency of side-effects.² One study has also shown than once-daily ritonavir at 100mg can still boost saquinavir levels when taken twice a day. This may help to reduce the pill burden and side-effects associated with ritonavir boosting, but it causes reductions in saquinavir exposure relative to twice-daily ritonavir, and cannot be recommended.³

Once-daily dosing of ritonavir-boosted saquinavir has also been studied in trials. Doses of 1600mg saquinavir with 100 or 200mg ritonavir are effective and produce adequate drug exposure.^{4 5 6} However, further research is required before this approach can be recommended.

Saquinavir should not be taken by patients with severe liver impairment.